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Restrictive Eating Disorders May Disrupt White Matter Development

Key findings

  • This cross-sectional MRI study examined whether ghrelin, normally an appetite-stimulating hormone, affected white matter health in 36 adolescent girls and women with anorexia nervosa (AN) or atypical AN (aAN) and 20 healthy controls (HC)
  • In individuals with AN/aAN, but not in HC, higher ghrelin levels were associated with decreased white matter in the fornix, the main fiber tract that connects the hippocampus with brain regions involved in energy balance and reward
  • Among the participants with AN/aAN, pubertal status moderated this relationship—higher levels of ghrelin were associated with decreased white matter only for those in the late/post-pubertal group
  • Pubertal status influenced the relationship between ghrelin and white matter even after adjustment for duration of AN/aAN

People with anorexia nervosa (AN) or atypical AN (aAN; similar behaviors as AN but without low weight) have abnormally high levels of ghrelin, a neuroprotective hormone expressed in the hippocampus. Normally, ghrelin stimulates the appetite, but the high ghrelin levels in individuals with restrictive eating disorders are not associated with increased eating. These disorders commonly have their onset during puberty, when white matter in the hippocampus and other parts of the brain is normally increasing.

Lauren Breithaupt, PhD, psychology clinical fellow, and Kamryn T. Eddy, PhD, co-director of the Eating Disorders Clinical and Research Program in the Department of Psychiatry at Massachusetts General Hospital, and Elizabeth Lawson, MD, of the Neuroendocrine Unit, and colleagues recently conducted the first study to assess the relationship between AN and white matter in the context of pubertal status. In Psychoneuroendocrinology, they report a relationship between higher ghrelin levels and decreased white matter in late-pubertal and adult females with AN or aAN.

Study Methods

The study participants were:

  • 36 adolescent girls and women with AN (n=22) or atypical AN (n=14) (AN/aAN group; age range 12-22)
  • 20 healthy controls of normal weight (HC group)

The participants underwent diffusion tensor imaging, a type of MRI. The metric of interest was fractional anisotropy (FA), which reflects white matter health.

AN/aAN vs. HC

There was no difference between the AN/aAN and HC groups with respect to FA in the fornix, the principal white matter fiber tract that connects the hippocampus to reward centers of the brain and regions that govern energy balance. Fasting plasma ghrelin levels were positively correlated with the Tanner stage of puberty in the AN/aAN group but not the HC group. Among individuals with AN/aAN, higher ghrelin levels were correlated with less FA (decreased white matter) in the fornix, but the opposite was true among HC.

Effect of Pubertal Status Within the AN/aAN Group

  • Early and mid-puberty: Ghrelin levels were high but were not associated with FA in the fornix. At these stages of puberty, high levels of ghrelin could represent an adaptive response to starvation and may help preserve white matter
  • Late and post-puberty: Ghrelin levels were even higher than at earlier stages, and they were significantly associated with decreased FA in the fornix

Pubertal status influenced the relationship between ghrelin and white matter even after the researchers controlled for the duration of AN/aAN.

Continued Scrutiny Needed

To improve detection of AN/aAN and treatment staging, the next step will be to understand how ghrelin affects white matter over time and after recovery from AN/aAN, and how those effects differ across pubertal stages.

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